The premalignant nature of oral leukoplakia has been established in clinicopathologic and follow-up investigations. These studies have identified several clinical and microscopic features with considerable predictive value. However, the role of viruses in this disease has only recently been addressed experimentally, presumably because new, more reliable detection techniques are available which have implicated Human Papillomaviruses (HPV) in the etiology of epithelial dysplasias and malignancies of the urogenital tract. Human papillomavirus antigens and DNA has been detected in carcinomas of the upper respiratory tract and oral leukoplakias. Long term goals are to fully understand the role of HPV in leukoplakia and this lesion's predisposition for malignant transformation. Secondarily the research will focus on a determination of predictive values and development of viral screening procedures for early detection of high-risk leukoplakias. Until recently, available methods for HPV detection were inadequate to readily establish the relative frequency of HPV in a large sampling of biopsied tissues or correlate presence of HPV (DNA) with clinical or microscopic features of high-risk lesions. A newly reported method, in vitro gene amplification via polymerase chain reaction will be used to determine the association between HPV and leukoplakia. The specific aims are: (1) Identify oligonucleotides to function as primers for amplification of HPV DNA in the polymerase chain reaction and detectors for the amplified DNA. (2) Determine the relative frequency of HPV DNA in tissue sections from 500 archival samples of oral leukoplakia. (3) Determine the correlation between presence of HPV DNA in leukoplakia samples and grade of epithelial dysplasia.